Increased expression of Fas ligand on Mycobacterium tuberculosis infected macrophages: A potential novel mechanism of immune evasion by Mycobacteriumtuberculosis?

We have studied the location and mechanism of apoptosis within the granulom as in the lungs at various stages of slowly progressive primary murine My c obacterium tuberculosis infection. Parallel sections were analyzed for dete ction of mycobacterial antigens, Fas, and Pas ligand (FasL) by immunohistoc hemistry, and for apoptotic cells by terminal deoxynucleotidyl-transferase- mediated dUTP-digoxigenin nick end labeling (TUNEL) method. The frequency o f apoptosis was high in the macrophage aggregates as compared to the lympho cyte aggregates and at the interface between them. Five to seven percent of the vacuolated macrophages in the granulomas expressed Fast intensely. The se cells contained large amounts of mycobacterial antigens. These findings suggest that M. tuberculosis infection can induce increased expression of F ast in a population of infected macrophages. As a consequence the infected macrophages will be protected from the attack of cytotoxic T cells and acti vation of bactericidal mechanisms by Th1 type lymphocytes. This constitutes a novel evasion mechanism for M. tuberculosis possibly explaining the chro nic course of infection.